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John Basile, DDS, DMSc.

Assistant Professor

Oncology and Diagnostic Sciences

mission

Similarities in the patterns of branching of blood vessels and nerves during growth and development have been acknowledged for some time. Biochemical and genetic confirmation of these anatomical findings has emerged recently with the identification that similar families of proteins control both axonal guidance in the nervous system and blood vessel development as well. My work focuses on two of these proteins, Semaphorin 4D (SEMA4D) and its receptor, Plexin-B1, and their role in tumor-induced angiogenesis (TIA), perineural invasion (PNI) and other features of agressive tumor growth.
 
We have observed that Plexin-B1 is highly expressed not only in nerves, but also in endothelial cells, where it promotes an angiogenic phenotype when bound by SEMA4D. Interestingly, we have shown that SEMA4D is overexpressed by the transformed cells of many different aggresive malignancies that exhibit profound TIA and PNI, characteristics correlated with an inability to arrest local spread of disease and eventual onset of metastasis. These findings suggest that the class IV semaphorins may play a role in enhanced invasive behavior, though the mechanism through which this occurs remains unknown. Currently, we are studying transcriptional control of SEMA4D, the pathways activated by Plexin-B1 and the biological relevance of these proteins in human malignancy. I believe our work will help to uncover an important mechanism of tumor cell behavior, thereby presenting new therapeutic targets in the treatment of advanced neoplasms.
 
PUBLICATIONS:

1) Zhou H., Yang Y., Binmadi N., Proia P., and Basile J. "The hypoxia-inducible factor-responsive proteins semaphorin 4D and vascular endothelial growth factor promote tumor growth and angiogenesis in oral squamous cell carcinoma." Exp Cell Res 2012 May 29 [Epub ahead of print].

2) Zhou H., Binmadi N., Yang Y., Proia P., and Basile J. "Semaphorin 4D cooperates with VEGF to promote angiogenesis and tumor progression." Angiogenesis 2012, Apr. 3 [Epub ahead of print]. 

3) Binmadi N., Yang Y., Zhou H., Proia P., Lin Y., Batista De Paula AM, Guimaraes AL, Poswar FO, Sundararajan D., and Basile J. "Plexin-B1 and Semaphorin 4D cooperate to promote perineural invasion in RhoA/ROK dependent manner." Amer J Pathol, 2012 Mar.; 180(3): 1232-42.

4) Yang Y., Zhou H., Binmadi N., Proia P., and Basile J. "Plexin-B1 activates NF-KB and IL-8 to promote a pro-angiogenic response in endothelial cells." PLoS ONE 2011 Oct.: 6(10): e25826. 

5) Binmadi N., Proia P., Zhou H., Yang Y., and Basile J., "Rho-mediated activation of PI(4)P5K and lipid second messengers is necessary for promotion of angiogenesis by Semaphorin 4D." Angiogenesis 2011 Sep.; 14(3): 309-19. 

6) Ma T., Jham B., Hu J., Friedman E., Basile J., Sodhi A., and Montaner S. "Viral G Protein-coupled Receptor Upregulates Angiopoietin-like 4 Promoting Angiogenesis and Vascular Permeability in Kaposi's sarcoma." Proc Natl Acad Sci U S A 2010 Aug. 10; 107(32): 14363-8.

7) Sakurai A., Gavard J., Annas-Linhares Y., Basile J., Amornphimoltham P., Palmby T., Yagi H., Zhang F., Randazzo P., Li X., Weigert R., and Gutkind JS. "Semaphorin 3E initiates anti-angiogenic signaling through Plexin-D1 by regulating Arf6 and R-Ras." Mol Cell Biol 2010 Jun.: 30(12): 3086-98.

8) Sun Q., Zhou H., Binmadi N., and Basile J. "Hypoxia inducible factor-1-mediated regulation of Semaphorin 4D affects tumor growth and vascularity." J Biol Chem 2009 Nov. 13; 284(46): 32066-74.

9) Basile J., Gavard J., Gutkind J.S.: “Plexin-B1 Utilizes RhoA and ROK to Promote the Integrin-dependent Activation of AKT and ERK, and Endothelial Cell Motility.” J Biol Chem 2007 Nov 30; 282(48): 34888-95.

10) Basile J., Holmbeck K., Bugge T.H., Gutkind J.S.: “MT1-MMP Controls Tumor-Induced Angiogenesis through the Release of Semaphorin 4D.” J Biol Chem 2007 Mar 2; 282(9): 6899-905.

11) Basile J., Castilho R.M., Williams V.P., Gutkind J.S.: “Semaphorin 4D Provides a Link between Axon Guidance Processes and Tumor-Induced Angiogenesis.” Proc Natl Acad Sci U S A 2006 Jun 13; 103(24): 9017-22.

12) Basile J., Afkhami T., Gutkind J.S.: “Semaphorin 4D-Mediated Activation of Plexin-B1 Induces Endothelial Cell Migration Through Activation of PYK2, Src and the PI3K-Akt pathway.” Mol Cell Biol 2005; 25: 6889-98.

13) Basile, J., Barac, A., Zhu, T., Guan, K., and Gutkind, J.S.: “Class IV Semaphorins Promote Angiogenesis by Stimulating Rho-Initiated Pathways through Plexin-B.” Ca Res 2004 Aug 1; 64: 5212-24.

EDUCATION AND TRAINING:

  • Degree: DDS, DMSc.
  • Residency: General Pratice Residency, Washington, DC, VA Hospital